Case of Primary Isolated Subconjunctival IgG4-Related Disease

Lee, Hyo Seok,Choi, Won,Kim, Ga Eon,Yoon, Kyung Chul Masson Pub. USA 2018 Cornea Vol.37 No.7

<P>Conclusions: IgG4-related disease is well known in the orbit and ocular adnexa, particularly the lacrimal gland. However, subconjunctival involvement should be recognized as a possible presentation for this entity.</P>

Apoptotic activity and antitumor efficacy of PEGylated TNF-related apoptosis-inducing ligand (TRAIL) in a Mia Paca-2 cell-xenografted mouse model

Byeon, H.J.,Choi, S.H.,Choi, J.S.,Kim, T.H.,Lee, E.S.,Lee, K.C.,Youn, Y.S. Masson Pub. USA, Inc 2014 BIOMEDICINE AND PHARMACOTHERAPY Vol.68 No.1

The purpose of this study was to demonstrate the apoptotic activity and antitumor effect of PEGylated tumor necrosis factor-related apoptosis-inducing ligand (PEG-TRAIL) in pancreatic carcinoma Mia Paca-2 cells and in Mia Paca-2 cell-xenografted mice. PEG-TRAIL was prepared using mPEG-aldehyde (Mw 5kDa). The apoptosis induced by PEG-TRAIL in Mia Paca-2 cells and in the tumors of Mia Paca-2 cell-xenografted mice was quantified by FACS analysis and using a TUNEL assay. Mia Paca-2 cell-xenografted BALB/c nu/nu mice were administered intratumoral injections of PEG-TRAIL (50μg/mouse/injection) every 3 days from day 0 (~4 weeks after xenografting) to day 15. Tumor volumes were measured every 3 days from day 0 to day 27. PEG-TRAIL displayed obvious apoptotic activity in Mia Paca-2 cells; the FACS signal was shifted to the apoptotic area and the cells exhibited green fluorescence indicating apoptosis in the TUNEL assay. Furthermore, PEG-TRAIL was found to suppress tumors in Mia Paca-2 cell-xenografted mice (tumor volumes: 183.9+/-134.1 for PEG-TRAIL vs. 1827.3+/-264.5 mm<SUP>3</SUP> for saline control). In addition, in vivo TUNEL assays of tumor tissues showed that the antitumor effect of PEG-TRAIL was due apoptosis. Our findings provide clear in vivo evidence of the antitumor potential of PEG-TRAIL in a Mia Paca-2 cell-xenografted mouse model based of pancreatic cancer.

Eyelid Tattooing Induces Meibomian Gland Loss and Tear Film Instability

Lee, Young Bok,Kim, Jin Joo,Hyon, Joon Young,Wee, Won Ryang,Shin, Young Joo Masson Pub. USA 2015 Cornea Vol.34 No.7

PURPOSE:: To investigate the changes of meibomian gland (MG) and tear film stability in subjects with eyelid tattoos. METHODS:: Forty female subjects were recruited. Ten subjects had eyelid tattoos and 30 subjects did not (control group). Tear film break-up time (TBUT) measurement and fluorescein staining were performed to evaluate the tear film. Distances between the eyelid tattoo and the MGs were measured and used to assign a tattoo score. The overall tattoo score, defined as the sum of upper and lower lid tattoo scores, was determined for each eye. MG loss was scored for each eyelid and added together to obtain the total “meiboscore” for each eye using meibography. Values between the tattoo and control groups were examined and compared. RESULTS:: The TBUT in the tattoo group (4.3 ± 0.9 seconds) was shorter than that in the control group (11.0 ± 4.3 seconds; P < 0.001). Corneal erosion, measured with fluorescein staining, was more severe in the tattoo group (1.6 ± 0.5) than that in the control group (0.2 ± 0.2; P < 0.001). MG loss was also more severe in the tattoo group (3.4 ± 1.5) than that in the control group (0.9 ± 0.6; P < 0.001). The total tattoo score was correlated with the total meiboscore (r = 0.852, P < 0.001, Spearman correlation coefficient). CONCLUSIONS:: Eyelid tattooing shortened TBUT, increased fluorescein staining, and induced MG loss. Therefore, eyelid tattooing increases tear film instability through MG disturbance, and patients could have exacerbated signs and symptoms of ocular surface disease.

Inhibitory Effect of Tranilast on Transforming Growth Factor-Beta-Induced Protein in Granular Corneal Dystrophy Type 2 Corneal Fibroblasts

Kim, Tae-im,Lee, Hun,Hong, Hye Kyoung,Kim, Kyu Seo,Choi, Seung-Il,Maeng, Yong-Sun,Kim, Eung Kweon Masson Pub. USA 2015 Cornea Vol.34 No.8

PURPOSE:: To investigate the effects of tranilast, an inhibitor of chemical mediators and fibroblast proliferation, on the expression of transforming growth factor-beta (TGF-&bgr;)-induced protein (TGFBIp) in wild-type (WT) and homozygous (HO) granular corneal dystrophy type 2 corneal fibroblasts. METHODS:: Cell proliferation and cytotoxicity were measured by Cell Counting Kit-8 and lactate dehydrogenase assay. Western blotting and real-time polymerase chain reaction were used to determine changes in the expression of TGFBIp and TGFBI mRNA. We determined the effects of tranilast on phosphorylated Smad2 (pSmad2) and pSmad3, wound-healing, and expression of alpha-smooth muscle actin (α-SMA), type I collagen, and integrins. RESULTS:: High concentrations of tranilast decreased proliferation of corneal fibroblasts but did not cause elevation of lactate dehydrogenase, except at 1.0 mM tranilast. TGF-&bgr; increased the expression of TGFBIp and TGFBI mRNA in WT and HO corneal fibroblasts. Cotreatment of corneal fibroblasts with tranilast and TGF-&bgr; reduced the levels of TGFBIp and TGFBI mRNA. In addition, application of tranilast reduced pSmad2 in WT and HO corneal fibroblasts and pSmad3 in HO corneal fibroblasts, both of which were increased initially by TGF-&bgr;. Tranilast delayed wound healing and reduced the expression of α-SMA, type I collagen, and some of integrins in WT and HO corneal fibroblasts. CONCLUSIONS:: Application of tranilast in WT and HO corneal fibroblasts inhibited the expression of TGFBIp by blocking TGF-&bgr; signaling. Thus, tranilast may be useful in delaying or preventing the recurrence of corneal opacity in TGFBI-linked corneal dystrophies if clinical studies confirm these findings.

Depression, Stress, Quality of Life, and Dry Eye Disease in Korean Women: A Population-Based Study

Na, Kyung-Sun,Han, Kyungdo,Park, Yong-Gyu,Na, Chul,Joo, Choun-Ki Masson Pub. USA 2015 Cornea Vol.34 No.7

PURPOSE:: To determine the relationship between dry eye disease (DED) and depressive symptoms in a nationally representative sample of Korean women. METHODS:: This population-based cross-sectional study comprised 6655 women (aged 19 years or older) participating in the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2011. Psychological problems associated with clinically diagnosed DED by ophthalmologists and symptoms of DED were assessed using questionnaires and surveys. Data were analyzed using logistic regression to determine the association of depression with allergic disease while controlling for age, lifestyle factors, and medical factors. RESULTS:: Among the participants, the prevalence of clinically diagnosed DED and its symptoms was 12.3% and 20.0%, respectively. Subjects with the diagnosis had a higher likelihood of experiencing severe psychological stress [odds ratio (OR), 2.5; 95% confidential interval (CI), 1.6–4.0], depressive mood (OR, 1.5; 95% CI, 1.1–2.0), anxiety/depression problems (OR, 1.5; 95% CI, 1.1–2.0) and tended to have a history of psychological counseling (OR, 1.8; 95% CI, 1.0–3.1). Subjects with symptoms of DED showed similar patterns. CONCLUSIONS:: There is a close association between depression, stress, and DED in women who have been clinically diagnosed with it or those presenting with its symptoms.

Comparison of Meibomian Gland Loss and Expressed Meibum Grade Between the Upper and Lower Eyelids in Patients With Obstructive Meibomian Gland Dysfunction

Eom, Youngsub,Choi, Kwang-Eon,Kang, Su-Yeon,Lee, Hyung Keun,Kim, Hyo Myung,Song, Jong Suk Masson Pub. USA 2014 Cornea Vol.33 No.5

PURPOSE:: The aim of this study was to compare meibomian gland loss (MGL) and expressed meibum grade between upper and lower eyelids in patients with obstructive meibomian gland dysfunction (MGD) and to evaluate the correlation between these 2 parameters and other clinical measurements. METHODS:: Twenty-six eyes of 26 patients with obstructive MGD were enrolled. Upper and lower MGLs were evaluated using noncontact meibography. Expressed meibum quality was assessed in 8 glands of the central third area of the upper and lower eyelids on a scale of 0 to 3 for each gland (total score range, 0–24). Tear film stability was evaluated based on tear break-up time (TBUT), and corneal staining was graded according to the National Eye Institute scale (range, 0–15). RESULTS:: The mean MGL in the lower eyelids (24.1% ± 10.8%) was significantly greater than that of the upper eyelids (11.2% ± 5.2%) (P < 0.001). The mean expressed meibum grade in the lower eyelids (16.5 ± 5.1) was also significantly larger than that of the upper eyelids (11.2 ± 5.2) (P < 0.001). MGL was significantly correlated with expressed meibum grade in both eyelids (r = 0.451, P = 0.021 in the upper eyelids; r = 0.626, P = 0.001 in the lower eyelids). The meibum grades of both the upper and lower eyelids were negatively correlated with TBUT and positively correlated with corneal staining score. However, the MGL in both the eyelids was not correlated with TBUT or with corneal staining score. CONCLUSIONS:: In patients with obstructive MGD, MGL and meibum grade in the lower eyelids were significantly greater than those of the upper eyelids. Although MGL and meibum quality showed a positive correlation with each other, TBUT and corneal staining score were significantly correlated with only meibum grade, and not with MGL.

Toluhydroquinone, the secondary metabolite of marine algae symbiotic microorganism, inhibits angiogenesis in HUVECs

Kim, N.H.,Jung, H.I.,Choi, W.S.,Son, B.W.,Seo, Y.B.,Choi, J.S.,Kim, G.D. Masson Pub. USA, Inc 2015 BIOMEDICINE AND PHARMACOTHERAPY Vol.70 No.-

Angiogenesis, the growth of new blood vessels from the existing ones, occurs during embryo development and wound healing. However, most malignant tumors require angiogenesis for their growth and metastasis as well. Therefore, inhibition of angiogenesis has been focused as a new strategy of cancer therapies. To treat cancer, there are marine microorganism-derived secondary metabolites developed as chemotherapeutic agents. In this study, we used toluhydroquinone (2-methyl-1,4-hydroquinone), one of the secondary metabolites isolated from marine algae symbiotic fungus, Aspergillus sp. We examined the effects of toluhydroquinone on angiogenesis using HUVECs. We identified that toluhydroquinone inhibited the activity of β-catenin and down-regulated Ras/Raf/MEK/ERK signaling which are crucial components during angiogenesis. In addition, the expression and activity of MMPs are reduced by the treatment of toluhydroquinone. In conclusion, we confirmed that toluhydroquinone has inhibitory effects on angiogenic behaviors of human endothelial cells, HUVECs. Our findings suggest that toluhydroquinone can be proposed as a potent anti-angiogenesis drug candidate to treat cancers.

Potential Value of Cellulose Synthesis Inhibitors Combined With PHMB in the Treatment of Acanthamoeba Keratitis

Moon, Eun-Kyung,Hong, Yeonchul,Chung, Dong-Il,Goo, Youn-Kyoung,Kong, Hyun-Hee Masson Pub. USA 2015 Cornea Vol.34 No.12

PURPOSE:: The aim of this study was to improve the cytopathic effect (CPE) of antiamebic agents by combining with cellulose synthesis inhibitor as an encystation inhibitor. METHODS:: Cellulose synthesis inhibitors, 2,6-dichlorobenzonitrile (DCB) and isoxaben were used to block encystation of Acanthamoeba during cultivation. Cultured human corneal epithelial (HCE) cells and Acanthamoeba were treated with polyhexamethylene biguanide (PHMB) combined with cellulose synthesis inhibitors to evaluate the CPE as an antiamebic agent. RESULTS:: 0.02% PHMB showed a 51.9% CPE on HCE cells within 30 minutes but exhibited significant toxic effects on Acanthamoeba. At a level of 0.00125%, PHMB had no significant CPEs on HCE cells, whereas 100 μM DCB and 10 μM isoxaben significantly inhibited the formation of the inner cyst wall of Acanthamoeba during encystation, and Acanthamoeba trophozoites failed to convert into mature cysts. Although a low concentration (0.00125%) of PHMB was used, the novel combinations with 100 μM DCB or 10 μM isoxaben had 23.4% or 18.7% additional amebicidal effects on Acanthamoeba. However, 100 μM DCB and 10 μM isoxaben had no CPEs on HCE cells. CONCLUSIONS:: The combination of cellulose synthesis inhibitors with low concentrations of PHMB reduced the CPE on HCE cells and improved the amebicidal effect on Acanthamoeba by inhibition of encystation.

Lapatinib enhances the cytotoxic effects of doxorubicin in MCF-7 tumorspheres by inhibiting the drug efflux function of ABC transporters

Chun, S.Y.,Kwon, Y.S.,Nam, K.S.,Kim, S. Masson Pub. USA, Inc 2015 BIOMEDICINE AND PHARMACOTHERAPY Vol.72 No.-

Increasing evidences indicate that cancer stem cells are resistant to chemotherapy due to their cell quiescence and the expression of ATP-binding cassette (ABC) transporters. In this study, we utilized tumorsphere cultures to seek better strategies to overcome chemoresistance since tumorsphere cultures have been used widely for the enrichment of cancer stem cells. We found that tumorspheres generated from MCF-7 human breast cancer cells exhibited high proportions of quiescent cells and expressed MDR-1 at elevated levels, leading to resistance to 5-fluorouracil, paclitaxel, and doxorubicin. Because the expression of EGFR/HER2 was increased in MCF-7 tumorspheres, we assessed the combinational effect of the dual ErbB1/ErbB2 inhibitor, lapatinib, with doxorubicin in tumorspheres. The results showed that inhibition of EGFR/HER2 signaling by lapatinib sensitized MCF-7 tumorspheres to doxorubicin by inhibiting the expression of the ABC transporters, MDR-1 and BCRP, and thus, enhancing the intracellular accumulation of doxorubicin. These findings suggest that combinations of lapatinib and cytotoxic anticancer drugs may offer an advantage for treating the drug-resistant cancers.

Protective effect of recombinant human erythropoietin in type II Gaucher disease patient cells by scavenging endoplasmic reticulum stress

Cha, J.R.,Kim, S.J.,Heo, T.H. Masson Pub. USA, Inc 2011 Biomedicine & pharmacotherapy Vol.65 No.5

Gaucher disease (GD) is an inherited disorder characterized by excessive accumulation of glucocerebroside in cells due to a non-functional glucocerebrosidase that is linked to programmed cell death pathways. Although clinical manifestations vary, type II GD is the most severe phenotype characterized by endoplasmic reticulum (ER) stress, neurological dysfunction, and anemia. Recombinant human erythropoietin (EPO) has been very popular for treating renal anemia and recently was shown to have extra-hematopoietic effects including neuroprotective properties. EPO's hematopoietic and neuroprotective effects prompted us to test EPO's beneficial action on type II GD patient cells. Initially, to examine the responsiveness of type II GD cells to EPO, the expression of the EPO receptor was determined at mRNA and protein levels. EPO effects on signaling pathways and ER stress in GD cells were also investigated. Finally, the proliferative effect of EPO on GD cells was verified. We found that EPO stimulated signaling pathways, enhanced the expression of glucocerebrosidase, reduced ER stress marker protein levels, and enhanced the proliferation rate of type II GD patient cells. This novel approach involving a beneficial role of EPO in GD should provide insights into new concepts for treating GD.